PMID- 10203685
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20131121
IS  - 1350-9047 (Print)
IS  - 1350-9047 (Linking)
VI  - 5
IP  - 10
DP  - 1998 Oct
TI  - Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice.
PG  - 858-66
AB  - Secreted forms of the beta-amyloid precursor protein (beta-APP) have 
      neuroprotective properties in vitro and may be involved in the containment of 
      neuronal excitation. To test whether loss of secreted forms of beta-APP (sAPPs) 
      may enhance excitotoxic responses, we injected mice homozygous for a targeted 
      mutation of the beta-APP gene (beta-APPDelta/Delta) intraperitoneally with kainic 
      acid. We found that in these mice, kainic acid induced seizures initiated 
      earlier, and acute mortality was enhanced compared to isogenic wild-type mice 
      independently from the callosal agenesis phenotype observed to occur at increased 
      frequency in APP mutant mice. Expression of c-fos in cortex and cingulate gyrus 
      was enhanced in beta-APPDelta/Delta mice, although the amount of structural 
      damage and apoptosis in the hippocampal pyramidal cell layer and cortex was 
      similar to that of controls. When cerebellar granule cell cultures and cortical 
      neuronal cultures were challenged with glutamate receptor agonists, the rates of 
      cell death and apoptosis of beta-APPDelta/Delta mice were indistinguishable from 
      those of controls. Therefore, deficiency of sAPPs causes facilitation of seizure 
      activity in the absence of enhanced cell death. Since enhanced seizures were 
      observed also in mice homozygous for a deletion of the entire beta-APP gene, this 
      phenotype results from a loss of APP rather than from a dominant effect of 
      APPDelta.
FAU - Steinbach, J P
AU  - Steinbach JP
AD  - Institute of Neuropathology, University Hospital, Zurich, Switzerland.
FAU - Muller, U
AU  - Muller U
FAU - Leist, M
AU  - Leist M
FAU - Li, Z W
AU  - Li ZW
FAU - Nicotera, P
AU  - Nicotera P
FAU - Aguzzi, A
AU  - Aguzzi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cell Death Differ
JT  - Cell death and differentiation
JID - 9437445
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 04079A1RDZ (Cytarabine)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Amyloid beta-Protein Precursor/deficiency/genetics/*physiology
MH  - Animals
MH  - Apoptosis
MH  - Brain/*pathology/physiopathology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology/physiology
MH  - Cytarabine/pharmacology
MH  - Death
MH  - Exons
MH  - Homozygote
MH  - In Situ Nick-End Labeling
MH  - Kainic Acid/toxicity
MH  - Mice
MH  - Mice, Knockout
MH  - Mutagenesis, Site-Directed
MH  - Neurons/cytology/drug effects/physiology
MH  - Proto-Oncogene Proteins c-fos/biosynthesis/genetics
MH  - Seizures/chemically induced/genetics/*physiopathology
EDAT- 1999/04/16 00:00
MHDA- 1999/04/16 00:01
CRDT- 1999/04/16 00:00
PHST- 1999/04/16 00:00 [pubmed]
PHST- 1999/04/16 00:01 [medline]
PHST- 1999/04/16 00:00 [entrez]
AID - 10.1038/sj.cdd.4400391 [doi]
PST - ppublish
SO  - Cell Death Differ. 1998 Oct;5(10):858-66. doi: 10.1038/sj.cdd.4400391.